Although bilirubin is found in stool and amniotic fluid, the major route of elimination of the fetus is through the placenta. All bilirubin found in the cord blood is of the unconjugated variety owing to the effective handling of bilirubin metabolism conjugation and excretion by the maternal liver and gall bladder. The mean cord blood bilirubin concentration is 1.8mg/dl regardless of the infant's gestational age or weight. As bilirubin production exceeds the newborn liver's capacity to conjugate and eliminate it, the plasma level begins to rise rapidly. Jaundice becomes noticeable when the serum concentration reaches three times the normal amount present in the serum.9
In the full-term infant, jaundice becomes apparent within two to four days after birth and lasts until the sixth day, reaching a peak concentration of 6 to 7 mg/dl. The preterm infant has cord blood levels similar to those of the term infant, but peak levels are higher, jaundice lasts longer, and levels peak later at five to seven days. Sixty-three percent of preterm infants achieve levels of 10 to 19 mg/dl, and 22 percent will reach levels > 15 mg/dl. Although the neonatal liver's conjugating mechanisms are reduced during the first few days of life, it possesses the ability to metabolize and excrete two-thirds to three-quarters of the bilirubin circulating throughout the body.
Both total serum bilirubin (TSB) and direct bilirubin (fraction conjugated with glucuronic acid) are commonly measured. In-office instruments are available for TSB measurements but may not be sufficiently accurate in the most important range (over 18 mg/dl). There are several instruments on the market that give transcutaneous bilirubin measurements. These may provide a strategy, in the future, for reliable office and home bilirubin assessments. However, the systems that are now available seem limited in their usefulness because they must be calibrated to a given laboratory, as well as calibrated for different skin types and colors.9
Although the major foci of research on neonatal jaundice have been toxicity and treatment, accurate and rapid measurement of elevated bilirubin concentration has also intrigued investigators. The standard clinical management of infants with jaundice includes visual estimates of the extent and serial estimation of serum bilirubin concentration by laboratory techniques using blood obtained by repetitive venous, arterial, or capillary puncture. Any mode of obtaining blood is a source of discomfort and infection. Transcutaneous bilirubinometry is a noninvasive and cost-effective alternative.
The practice of noninvasive bilirubin measurement in newborns predates our recognition of bilirubin as the agent responsible for jaundice. The device most commonly used is the human eye, with or without the aid of a reference device or a hand-held battery-powered meter. Simple visual estimates for the presence or absence of jaundice are made daily by pediatricians to aid in the decision to test serum bilirubin levels. The visual estimate is redefined by classifying the dermal zone of jaundice based on the phenomenon of cephalocaudal progression.
Jaundice in zone one (from head to neck and the level of the clavicle) translates approximately to a serum bilirubin concentration of 5 mg/dl; in zone two (from the clavicle to the umbilicus), to 6 – 8 mg/dl; in zone three (from the umbilicus to the knees), 9 – 12 mg/dl; in zone four (from the knees to the ankles), to 13 – 15 mg/dl; and in zone five (the palms and soles), to over 15 mg/dl. A second refinement of the visual estimate is the use of a reference device. In 1925 Rowntree and Brown used a tintometer, while in 1960, Gosset described the use of the Ingram Icterometer to gauge the depth of jaundice in newborns.
Jaundice needing treatment is generally calculated based on the amount of bilirubin and the age of the infant. A calculator, like the one available on www.bilitool.org, can calculate the infant's risk.10
A more sophisticated device is the Minolta/Air Shields Jaundice Meter. It works via the principle of skin reflectance, which assumes that subcutaneous bilirubin is correlated linearly to serum bilirubin. The ability to estimate serum bilirubin values can be simplified by using the compartmental model. The relationship between bilirubin concentrations in the subcutaneous tissue compartment and the blood compartment is governed by rate constants that describe the rate of entry and exit of bilirubin from one compartment to another.
To obtain a satisfactory correlation between these two values, the serum bilirubin measurements and the cutaneous bilirubin measurement must be accurate. The two compartments and the kinetics of the transfer of bilirubin to and from each compartment must be similar for every infant.
In studies of jaundice meters' precision, several investigators have found them less precise for low serum bilirubin levels. Still, others have suggested that the jaundice meter's accuracy may be compromised at higher serum bilirubin concentrations. Accuracy may also be compromised by the variability of individual meters, the influence of operator technique, and the presence of alcohol on the meter probe or the baby's skin. The accuracy of jaundice meters is a function of precision and the presence or absence of bias in the form of additional or interfering race-dependent skin chromogens and the presence of bruising or birthmarks. Factors such as exchange transfusion, phototherapy, body site measurement, albumin concentration, pH, and gestational and chronological age can alter results.
To avoid some of the know problems with transcutaneous devices, computerized photo-sensors that take advantage of skin tone information are being tested. Instead of registering the simple change in skin color caused by bilirubin, the meter can measure minute alterations in any one of a vast array of human skin types. This patient-specific analysis takes account of race and skin perfusion and, in effect, allows the computer to detect bilirubin below the surface.11
Surprisingly, phototherapy does not seem to interfere with the measurement, even though infants, while being treated, appear less jaundiced to the eye. The value of screening tools ultimately rests on the clinician's need to measure bilirubin in the newborn. The trends toward extremely early discharge after delivery, cost containment, and decreases in medical interventions should increase our requirements for simple safe methods of determining which infants have more than just physiologic jaundice.